The Pathology Core (Core B) will support multiple projects within the program by providing human tissues for esearch. The director of the Pathology Core, Dr. Andrea Richardson, is a board certified pathologist with a specialty in breast pathology. She is director of the breast tissue bank at Brigham and Women's Hospital and oversees the collection, storage, processing and analysis of breast tissues. The breast tissue repository at BWH holds over 1500 breast tumor specimens with full pathology annotation. Many of these specimens have undergone extensive molecular analysts including gene expression array profiling, SNP array genotyping, and are also represented in paraffin-embedded tissue microarrays. In addition to tumor tissues, he BWH repository also collects normal breast tissue specimens from breast reduction surgeries. These normal tissues are stored as frozen samples or can be provided as fresh samples for isolation of normal organoids or breast stem cells. The pathology core will provide normal breast tissue for stem cell studies (Polyak) and for 3-D organoid cultures (Brugge). Fresh tumor samples will be provided to establish primary tumor xenografts in mice Weinberg). In addition, Dr. Richardson will participate in the pathologic comparisons, both molecular and histology, between the parent human tumors and the resultant xenografts. Gene expression array data obtained from human tumors will be used in system interaction analyses of BRCA1 related pathways (Livingston). Dr. Richardson will provide both tissue and scientific expertise to analyze frozen tumor specimens and paraffin tissue microarrays for the expression of BRCA1 gene products, including IRIS (Livingston).RELEVANCE (See instructions): Research using actual human breast tissue and breast tumor material will hopefully provide the most relevant answers to pathogenesis and tumor behavior of breast cancer in women. PROJECT/